Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO)

Alipour, Faranak; Riyahi, Niknam; Safaroghli‐Azar, Ava; Sari, Soyar; Zandi, Zahra; Bashash, Davood

doi:10.1016/j.biocel.2019.105615

Cited by 17 publications

(16 citation statements)

References 45 publications

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“…Noteworthy, when we blocked the expression of c-Myc using 10058-F4, the anti-cancerous impact of AT7519 was boosted strenuously; indicative of the weakening impact of c-Myc on the effectiveness of CDK inhibitor. Other studies also declared that c-Myc blockage in leukemic cells can be an effective approach to ameliorate the cytotoxic effect of anti-cancer agents while reducing their toxic concentrations (27)(28)(29)(30)(31).…”

Section: Discussionmentioning

confidence: 99%

Inhibitor of Multi-cyclin-dependent Kinases (AT7519) Reduced Survival of U937 Leukemic Cells and Enhanced Anti-leukemic Effect of Vincristine: A Highlight to CDK Inhibition Efficacy in Acute Leukemia

Moraddahande¹,

Houjghan²,

Yousefi³

et al. 2021

Int J Cancer Manag

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Background: The conservative character of the cell cycle outlined that any dysregulation in the regulatory components of this process in normal cells opens a gate toward neoplastic transformation. Objectives: Given the critical role of cyclin-dependent kinases (CDKs) in cancer pathogenesis and based on their frequent aberrancy in human leukemia, the present study aimed at evaluating the suppressive effect of a multi-CDK inhibitor AT7519 on acute myeloid leukemia-derived U937 cells. Methods: To assess the anti-leukemic effects of the inhibitor on acute myeloid leukemia (AML) cells, we used MTT and trypan blue assays. Flow cytometric analysis and q-RT-PCR were also applied to evaluate the impact of AT7519 on cell cycle and apoptosis. Results: The results suggested that suppression of CDK in U937 cells hampered the proliferation of leukemic cells through a G2/M arrest mediated by p21 gene. Additionally, the anti-survival impact of AT7519 on these cells was shown to be along with the apoptosis initiation not only through the increment of pro-apoptotic gene expression but also through diminishing the mRNA levels of both Pin1 and Survivin. Notably, the potent anti-leukemic property of this agent has become more prominent when we found that the blockage of CDKs in AML cells could synergize with the cytotoxic effect of vincristine (VCR). To the best of our knowledge, little is known about the molecular mechanisms of resistance to AT7519 and we proposed that the effectiveness of this agent was partially attenuated through either c-Myc or autophagy activation in U937 cells. Conclusions: This study suggests that the pharmacological targeting of CDKs could probably unwind the complexity of therapeutic obstacles on the way of acute leukemia, either in the context of mono- or combined-modal strategy.

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Section: Discussionmentioning

confidence: 99%

Inhibitor of Multi-cyclin-dependent Kinases (AT7519) Reduced Survival of U937 Leukemic Cells and Enhanced Anti-leukemic Effect of Vincristine: A Highlight to CDK Inhibition Efficacy in Acute Leukemia

Moraddahande¹,

Houjghan²,

Yousefi³

et al. 2021

Int J Cancer Manag

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“…Buparlisib is an oral pan-PI3K inhibitor that its efficacy has been tested in a wide range of solid [147][148][149] and hematologic malignancies. [150][151][152][153][154] Recently, this drug has been entered into Phase III clinical trials for the treatment of breast cancer (NCT01633060).…”

Section: Buparlisibmentioning

confidence: 99%

The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma: Possibilities for therapeutic interventions either as single agents or in combination with conventional therapies

Dilmaghani

Safaroghli‐Azar

Pourbagheri‐Sigaroodi

et al. 2021

IUBMB Life

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The latest advances in the sequencing methods in head and neck squamous cell carcinoma (HNSCC) tissues have revolutionized our understanding of the disease by taking off the veil from the most frequent genetic alterations in the components of the oncogenic pathways. Among all the identified alterations, aberrancies in the genes attributed to the phosphoinositide 3-kinases (PI3K) axis have attracted special attention as they were altered in more than 90% of the tissues isolated from HNSCC patients. In fact, the association between these aberrancies and the increased risk of cancer metastasis suggested this axis as an "Achilles Heel" of HNSCC, which may be therapeutically targeted. The results of the clinical trials investigating the therapeutic potential of the inhibitors targeting the components of the PI3K axis in the treatment of HNSCC patients, either alone or in a combined-modal strategy, opened a new chapter in the treatment strategy of this malignancy. The present study aimed

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“…Buparlisib is most widely used in breast cancer and HNSCC. In addition to affecting the growth and cell cycle arrest of breast cancer cells (64,65), buparlisib can also be combined with the inhibition of the c-Myc-mediated human telomerase reverse transcriptase (hTERT) to enhance the arsenic trioxide (ATO)-induced anti-proliferative effect (66). In a study on colorectal cancer, Solberg et al (67) found that buparlisib can block HCT-15 cells at the G 1 phase, accompanied by a decrease in c-Myc and cyclin D1 and increase in cyclin-dependent kinase inhibitor (CDKN) 1A and CDKN1B.…”

Section: Buparlisib Induces Apoptosis and Inhibits Proliferationmentioning

confidence: 99%

Research update on the anticancer effects of buparlisib (Review)

Xing

Yang

et al. 2021

Oncol Lett

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Buparlisib is a highly efficient and selective PI3K inhibitor and a member of the 2,6-dimorpholinopyrimidine-derived family of compounds. It selectively inhibits four isomers of PI3K, PI3Kα, PI3Kβ, PI3Kγ and PI3Kδ, by competitively binding the lipid kinase domain on adenosine 5'-triphosphate (ATP), and serves an important role in inhibiting proliferation, promoting apoptosis and blocking angiogenesis, predominantly by antagonizing the PI3K/AKT pathway. Buparlisib has been confirmed to have a clinical effect in patients with solid tumors and hematological malignancies. A global, phase II clinical trial with buparlisib and paclitaxel in head and neck squamous cell carcinoma has now been completed, with a manageable safety profile. Buparlisib currently has fast-track status with the United States Food and Drug Administration. The present review examined the biochemical structure, pharmacokinetic characteristics, preclinical data and ongoing clinical studies of buparlisib. The various mechanisms of influence of buparlisib in tumors, particularly in preclinical research, were summarized, providing a theoretical basis and direction for basic research on and clinical treatment with buparlisib.

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Inhibition of PI3K pathway using BKM120 intensified the chemo-sensitivity of breast cancer cells to arsenic trioxide (ATO)

Cited by 17 publications

References 45 publications

Inhibitor of Multi-cyclin-dependent Kinases (AT7519) Reduced Survival of U937 Leukemic Cells and Enhanced Anti-leukemic Effect of Vincristine: A Highlight to CDK Inhibition Efficacy in Acute Leukemia

Inhibitor of Multi-cyclin-dependent Kinases (AT7519) Reduced Survival of U937 Leukemic Cells and Enhanced Anti-leukemic Effect of Vincristine: A Highlight to CDK Inhibition Efficacy in Acute Leukemia

The PI3K/Akt/mTORC signaling axis in head and neck squamous cell carcinoma: Possibilities for therapeutic interventions either as single agents or in combination with conventional therapies

Research update on the anticancer effects of buparlisib (Review)

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